Intracerebroventricularly applied peptidase inhibitors increase endogenous angiotensin levels.
Rats received the aminopeptidase inhibitors amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) via intracerebroventricular infusion in various combinations, i.e. PL alone, AM + BE, and a cocktail consisting of AM + BE + PL. Blood pressure responses were recorded and a postinfusion sample of cerebrospinal fluid (CSF) was radioimmunoassayed for endogenous angiotensin levels. Results indicate that CSF angiotensin was increased approximately 1.5x over control levels when PL was infused; a 2.5x increase accompanied AM + BE administration; and a 10.3x elevation was measured when all 3 inhibitors were infused as a cocktail. Concomitant elevations in blood pressure accompanied increased concentrations of angiotensin. We conclude that endogenous levels of angiotensin can be significantly increased in the ventricular space when a combination of these inhibitors is utilized to protect both the amino and carboxyl terminals of the angiotensin molecule from enzymatic degradation.
Batt
C M
CM
Department of Psychology, Washington State University, Pullman 99164-6520.
Jensen
L L
LL
Hanesworth
J M
JM
Harding
J W
JW
Wright
J W
JW
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000804:Angiotensin II / Q000134:cerebrospinal fluid*; D000805:Angiotensin III / Q000134:cerebrospinal fluid*; D000818:Animals; D000900:Anti-Bacterial Agents; D001794:Blood Pressure / Q000187:drug effects; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides; D011480:Protease Inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D010455:Peptides; D011480:Protease Inhibitors; D000804:Angiotensin II; D000805:Angiotensin III; C016977:amastatin; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; D015097:3-Mercaptopropionic Acid; D002268:Carboxypeptidases; D007930:Leucine; C012211:ubenimex